Degeneration of the intervertebral disc and facet cartilage are among the most common causes of back pain. Degradation of the extracellular matrix of these tissues results from an imbalance in matrix catabolism and anabolism. Multiple processes contribute to degradation of the matrix including increased inflammation, increased catabolism and decreased anti-catabolism. Mechanical loading in the spine has been shown to mediate these processes to accelerate degeneration or to promote repair;thresholds of biological response vary as a function of loading duration, frequency, and magnitude. This project aims to explore the effect of range-of- motion (ROM) in 6 degree-of-freedom (DOF) motion on inflammatory and catabolic markers in viable rabbit functional spinal units (FSUs). Using a novel ex-vivo mechanobiological system coupled with an existing robot-based spine testing system, amplitudes will be applied in DOF that reflect patterns of loading used in complementary and alternative medicine (CAM) motion- based therapies like chiropractic mobilization and yoga. Specifically, coupled axial rotation with posterior-anterior translation (simulating chiropractic mobilization loading patterns) and flexion- extension ROM (simulating yoga loading patterns) will be varied to elucidate the effect of amplitude on biological mediators. Biological outcomes following loading will include relative gene expression by real time RT-PCR of inflammatory, catabolic and anti-catabolic genes, protein expression and localization by immunohistochemistry of catabolic and anti-catabolic proteins, and media concentrations of released cytokines and matrix fragments by ELISA. Based on classical mobilization paradigms, it is hypothesized that repetitive (15 s at 1 Hz, 5x) complex low amplitude loading (2.50/0-0.25mm) will reduce inflammatory mediators and complex high amplitude loading (50/0.25-0.5mm) will improve the balance of matrix homeostasis by reducing catabolic or increasing anti-catabolic markers. In flexion-extension, it is hypothesized that increased ROM will similarly benefit matrix homeostasis by reducing catabolic or increasing anti-catabolic outcomes. A mechanistic understanding of the influence of mechanical loading patterns relevant to CAM motion-based therapies on load-bearing tissues in the spine will inform clinical strategies and studies that aim to rationally prescribe motion therapy for specific patient groups. Ultimately, th clinical impact of a mechanistic characterization of CAM approaches to back pain would allow for enhancement of current treatment by rational combinations of CAM therapies or integrating CAM approaches with conventional care for optimal, specific treatment.